Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study.

Abstract

The temporal development of autoantibodies was studied in 1,353 offspring of parents with type 1 diabetes. Islet cell antibodies (ICAs) and autoantibodies to insulin (IAAs), glutamic acid decarboxylase, and IA-2 were measured at birth, 9 months, 2 years, and 5 years of age. At birth, no offspring had islet autoimmunity other than maternally acquired antibodies, which were shown to influence antibody prevalence up to age 6 months. Antibodies detected thereafter were likely to represent a true de novo production, since prevalences were the same for offspring from mothers and fathers with diabetes, antibodies detected at 9 months were almost always confirmed in the 2-year sample and were associated with an increased likelihood of having or developing other antibodies. By 2 years of age, autoantibodies appeared in 11% of offspring, 3.5% having more than one autoantibody. IAAs were detected most frequently, and few had autoantibodies in the absence of IAAs. In 23 offspring with multiple islet autoantibodies, IAAs preceded other antibodies in 10 cases and were first detected concurrently with other antibodies in 12 and after detection of other antibodies in 1. Development of additional antibodies and changes in levels, including decline of IAAs at older age, was frequent. Nine children, all with IAAs and ICAs, developed diabetes. Overall cumulative risk for disease by 5 years of age was 1.8% (95% CI 0.2-3.4) and was 50% (95% CI 19-81) for offspring with more than one autoantibody in their 2-year sample. Autoimmunity associated with childhood diabetes is an early event and a dynamic process. Presence of IAAs is a consistent feature of this autoimmunity, and IAA detection can identify children at risk.

Fetal growth is increased by maternal type 1 diabetes and HLA DR4-related gene interactions

“…Subjects Children followed prospectively from birth in the German BABYDIAB [16][17][18] and BABYDIET [19] studies were included. Recruitment into the studies began in 1989 (BABYDIAB) and 2000 (BABYDIET).…”

Genetic linkage and association studies of Type I diabetes: challenges and rewards

“…Either way, the presence of antibodies to islet cell components (especially multiple autoantibodies at high titres) is strongly associated with risk of progressing to clinical diabetes, both in relatives of Type I diabetic patients [7] and in the general population [28]. Recent studies have shown that autoantibodies occur even in infants and young children who later develop diabetes, suggesting that the autoimmune process could begin very early in life, perhaps prenatally [8,29,30]. Because autoantibodies are biological markers for preclinical diabetes, it is important to know whether these autoantibodies show evidence for genetic determination, or whether they merely reflect the presence of non-genetic diabetes-predisposing factors (such as viruses that damage beta cells).…”

The use of phage display to distinguish insulin autoantibody (IAA) from insulin antibody (IA) idiotypes

“…IAA is of particular interest as markers for beta-cell disease, and is the first of the islet-related antibodies to appear during early insulitis [4]. Insulin binding antibodies can nevertheless be isolated from healthy people, from patients with autoimmune diseases other than Type 1 diabetes [5], and following certain medications where their presence reduces the clinical specificity of the test for diabetes.…”